We have found that the binding site of 3H-prazosin, a selective ligand for Alpha1-adrenergic recognition sites is significantly lower in the frontal cortex of the genetically epilepsy prone rats (GEPR), as compared with normal Sprague Dawley rats. Scratched analysis reveals a decrease in the Bmax of 3H-prazosin binding with no change int he apparent KD, suggesting that there are fewer Alpha1-adrenergic recognition sites in the frontal cortex of the GEPR. This abnormality is assocaited with a reduced capacity of norepinephrine (NE) to stimulate 3H-inositol-l-phosphate formation in frontal cortex slices prelabeled with 3H-inositol. No significant differences in 3H-prazosin binding as well as NE-stimulated 3H-inositol-l-phosphate formation have been observed in other brain regions including hippocampus, corpus striatum and inferior colluculus. These results indicate that a deficit in the X1-adrenergic receptor system in the frontal cortex may play a role in the seizure process in the GEPR.